Patients having reduced immunity such as those undergoing chemical therapy for cancer, recovering from organ transplants, and suffering from AIDS are at a great risk of fungal infection, mostly by opportunistic pathogens such as Candida spp., Aspergillus spp. and Cryptococcus neoformans. The antifungals available in the market are not effective in such cases because of the problems of toxicity and narrow spectrum of activity.
There have been developed a number of antifungal compounds, e.g., orally administrable triazole derivatives represented by fluconazole (GB Patent No. 2099818), itraconazole (U.S. Pat. No. 4,267,179) and voriconazole (EP Patent No. 0440372). None of them, however, show inhibitory activity sufficiently effective for controlling the opportunistic fungi which cause fatal infection in such patients described above.
Many of the conventional antifungals have a structure comprising a triazole having an additional heterocyclic substituent. Disclosed are, for example, triazole derivatives having: a five-membered isoxazole (EP Patent No. 0241232); a triazolone moiety (EP Patent No. 0659751); and a pyrazole ring (Japanese Patent No. 3415865 and International Patent Publication No. WO 2001/79196).
However, the conventional derivatives disclosed in the above-mentioned patents are not completely satisfactory in treating severe fugal infection.